The mechanism of action of CapZ in myocardial Z-discs

Aiello, David Louis
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University of Guelph

Cardiac myofilaments play an enormous role in proper cardiac function and have been the area of focus in relation to heart failure for some time. It is only recently that some focus has shifted to Z-disc proteins. Historically, Z-disc proteins have been regarded as functionally dormant, structural elements of cardiac sarcomeres. Recently, evidence from our group has shown that CapZ, a Z-disc protein, plays a role in intracellular signaling and mechanotransduction, aside from its structural role, and may be a promising therapeutic target in heart failure. In the present study, we investigated the role of CapZ and its involvement in troponin binding, cross-bridge binding, and dephosphorylation regulation of protein phosphatase type-1[alpha] (PP1[alpha]). We report that in CapZ-deficient myofilaments, Tn is more easily extracted when compared to normal myofilaments. We also show that myofilaments deficient in CapZ are more easily 'turned on' and 'turned off of the strong cross-bridge state than normal myofilaments. Finally, we show that the disruption in PP1[alpha] control seen in CapZ-deficient myofilaments is not a desensitization to covalent modification.

Cardiac myofilaments, Cardiac function, Heart failure, Z-disc proteins, Cross-bridge binding